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Intestinal Npt2b Plays a Major Role in Phosphate Absorption and Homeostasis

Renal and Endocrine Sciences Group, Genzyme Corporation, Framingham, Massachusetts

Correspondence: Dr. Susan C. Schiavi, 49 New York Avenue, Framingham, MA 01701. Phone: (508) 270-2354; Fax: (508) 271-4955; E-mail: susan.schiavi{at}genzyme.com

Received for publication May 30, 2009. Accepted for publication July 1, 2009.

Intestinal phosphate absorption occurs through both a paracellular mechanism involving tight junctions and an active transcellular mechanism involving the type II sodium-dependent phosphate cotransporter NPT2b (SLC34a2). To define the contribution of NPT2b to total intestinal phosphate absorption, we generated an inducible conditional knockout mouse, Npt2b^–/– (Npt2b^fl/fl:Cre^+/–). Npt2b^–/– animals had increased fecal phosphate excretion and hypophosphaturia, but serum phosphate remained unchanged. Decreased urinary phosphate excretion correlated with reduced serum levels of the phosphaturic hormone FGF23 and increased protein expression of the renal phosphate transporter Npt2a. These results demonstrate that the absence of Npt2b triggers compensatory renal mechanisms to maintain phosphate homeostasis. In animals fed a low phosphate diet followed by acute administration of a phosphate bolus, Npt2b^–/– animals absorbed approximately 50% less phosphate than wild-type animals, confirming a major role of this transporter in phosphate regulation. In vitro analysis of active phosphate transport in ileum segments isolated from wild-type or Npt2b^–/– mice demonstrated that Npt2b contributes to >90% of total active phosphate absorption. In summary, Npt2b is largely responsible for intestinal phosphate absorption and contributes to the maintenance of systemic phosphate homeostasis.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673